Entorhinal-based path integration selectively predicts midlife risk of Alzheimer's disease.

INTRODUCTION: Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD. METHODS: We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function. RESULTS: Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi-risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior-medial EC. DISCUSSION: Altered PI may represent the transition point from at-risk state to disease manifestation in AD, prior to impairment in other cognitive domains.

Firing rate adaptation affords place cell theta sweeps, phase precession, and procession.

Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here, we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between 'bimodal cells' showing interleaved phase precession and procession, and 'unimodal cells' in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells' firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.

Overestimation in angular path integration precedes Alzheimer's dementia.

Path integration (PI) is impaired early in Alzheimer's disease (AD) but reflects multiple sub-processes that may be differentially sensitive to AD. To characterize these sub-processes, we developed a novel generative linear-angular model of PI (GLAMPI) to fit the inbound paths of healthy elderly participants performing triangle completion, a popular PI task, in immersive virtual reality with real movement. The model fits seven parameters reflecting the encoding, calculation, and production errors associated with inaccuracies in PI. We compared these parameters across younger and older participants and patients with mild cognitive impairment (MCI), including those with (MCI+) and without (MCI-) cerebrospinal fluid biomarkers of AD neuropathology. MCI patients showed overestimation of the angular turn in the outbound path and more variable inbound distances and directions compared with healthy elderly. MCI+ were best distinguished from MCI- patients by overestimation of outbound turns and more variable inbound directions. Our results suggest that overestimation of turning underlies the PI errors seen in patients with early AD, indicating specific neural pathways and diagnostic behaviors for further research.

Visual information processing through the interplay between fine and coarse signal pathways.

Object recognition is often viewed as a feedforward, bottom-up process in machine learning, but in real neural systems, object recognition is a complicated process which involves the interplay between two signal pathways. One is the parvocellular pathway (P-pathway), which is slow and extracts fine features of objects; the other is the magnocellular pathway (M-pathway), which is fast and extracts coarse features of objects. It has been suggested that the interplay between the two pathways endows the neural system with the capacity of processing visual information rapidly, adaptively, and robustly. However, the underlying computational mechanism remains largely unknown. In this study, we build a two-pathway model to elucidate the computational properties associated with the interactions between two visual pathways. Specifically, we model two visual pathways using two convolution neural networks: one mimics the P-pathway, referred to as FineNet, which is deep, has small-size kernels, and receives detailed visual inputs; the other mimics the M-pathway, referred to as CoarseNet, which is shallow, has large-size kernels, and receives blurred visual inputs. We show that CoarseNet can learn from FineNet through imitation to improve its performance, FineNet can benefit from the feedback of CoarseNet to improve its robustness to noise; and the two pathways interact with each other to achieve rough-to-fine information processing. Using visual backward masking as an example, we further demonstrate that our model can explain visual cognitive behaviors that involve the interplay between two pathways. We hope that this study gives us insight into understanding the interaction principles between two visual pathways.

Path integration selectively predicts midlife risk of Alzheimer's disease.

The entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration, we predicted that path integration impairment would represent the first behavioural change in adults at-risk of AD. Using immersive virtual reality, we found that midlife path integration impairments predicted both hereditary and physiological AD risk, with no corresponding impairment on tests of episodic memory or other spatial behaviours. Impairments related to poorer angular estimation and were associated with hexadirectional grid-like fMRI signal in the posterior-medial EC. These results indicate that altered path integration may represent the transition point from at-risk state to disease onset in AD, prior to impairment in other cognitive domains.

Neural feedback facilitates rough-to-fine information retrieval.

Categorical relationships between objects are encoded as overlapped neural representations in the brain, where the more similar the objects are, the larger the correlations between their evoked neuronal responses. These representation correlations, however, inevitably incur interference when memories are retrieved. Here, we propose that neural feedback, which is widely observed in the brain but whose function remains largely unknown, contributes to disentangle neural correlations to improve information retrieval. We study a hierarchical neural network storing the hierarchical categorical information of objects, and information retrieval goes from rough-to-fine, aided by the push-pull neural feedback. We elucidate that the push and the pull components of the feedback suppress the interferences due to the representation correlations between objects from different and the same categories, respectively. Our model reproduces the push-pull phenomenon observed in neural data and sheds light on our understanding of the role of feedback in neural information processing.

A brain-inspired computational model for spatio-temporal information processing.

Spatio-temporal information processing is fundamental in both brain functions and AI applications. Current strategies for spatio-temporal pattern recognition usually involve explicit feature extraction followed by feature aggregation, which requires a large amount of labeled data. In the present study, motivated by the subcortical visual pathway and early stages of the auditory pathway for motion and sound processing, we propose a novel brain-inspired computational model for generic spatio-temporal pattern recognition. The model consists of two modules, a reservoir module and a decision-making module. The former projects complex spatio-temporal patterns into spatially separated neural representations via its recurrent dynamics, the latter reads out neural representations via integrating information over time, and the two modules are linked together using known examples. Using synthetic data, we demonstrate that the model can extract the frequency and order information of temporal inputs. We apply the model to reproduce the looming pattern discrimination behavior as observed in experiments successfully. Furthermore, we apply the model to the gait recognition task, and demonstrate that our model accomplishes the recognition in an event-based manner and outperforms deep learning counterparts when training data is limited.

Unsupervised Few-Shot Feature Learning via Self-Supervised Training.

Learning from limited exemplars (few-shot learning) is a fundamental, unsolved problem that has been laboriously explored in the machine learning community. However, current few-shot learners are mostly supervised and rely heavily on a large amount of labeled examples. Unsupervised learning is a more natural procedure for cognitive mammals and has produced promising results in many machine learning tasks. In this paper, we propose an unsupervised feature learning method for few-shot learning. The proposed model consists of two alternate processes, progressive clustering and episodic training. The former generates pseudo-labeled training examples for constructing episodic tasks; and the later trains the few-shot learner using the generated episodic tasks which further optimizes the feature representations of data. The two processes facilitate each other, and eventually produce a high quality few-shot learner. In our experiments, our model achieves good generalization performance in a variety of downstream few-shot learning tasks on Omniglot and MiniImageNet. We also construct a new few-shot person re-identification dataset FS-Market1501 to demonstrate the feasibility of our model to a real-world application.